Overcoming Resistance for a More Rational Therapeutic Approach.

is an underappreciated source of morbidity and mortality among gram-negative pathogens. Effective treatment options with acceptable toxicity profiles are limited. Phenotypic susceptibility testing via commercial automated test systems is problematic and no Food and Drug Administration breakpoints are approved for any of the first-line treatment options for . The lack of modern pharmacokinetic/pharmacodynamic data for many agents impedes dose optimization, and the lack of robust efficacy and safety data limits their clinical utility. Levofloxacin has demonstrated similar efficacy to trimethoprim-sulfamethoxazole, although rapid development of resistance is a concern. Minocycline demonstrates the highest rate of in vitro susceptibility, however, evidence to support its clinical use are scant. Novel agents such as cefiderocol have exhibited promising activity in preclinical investigations, though additional outcomes data are needed to determine its place in therapy for . Combination therapy is often employed despite the dearth of adequate supporting data.